CN101468946B - Preparation technique of 5-methoxy-2-tetralone - Google Patents
Preparation technique of 5-methoxy-2-tetralone Download PDFInfo
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- CN101468946B CN101468946B CN2007103053265A CN200710305326A CN101468946B CN 101468946 B CN101468946 B CN 101468946B CN 2007103053265 A CN2007103053265 A CN 2007103053265A CN 200710305326 A CN200710305326 A CN 200710305326A CN 101468946 B CN101468946 B CN 101468946B
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Abstract
The invention discloses technology for preparing 5-methoxyl-2-tetralone, which belongs to a method for preparing tetralone compounds and is technology for preparing the 5-methoxyl-2-tetralone by using sodium metals to reduce 1,6-dimethoxy benzene in an alcohol medium and an ammonia medium at a temperature of between 15 and 35 DEG C, wherein the weight ratio of anhydrous alcohol to the 1,6-dimethoxy benzene during reduction is 6.0-9.0:1; the weight ratio of an ammonia liquid to the 1,6-dimethoxy benzene is 0.05-0.4:1; the weight ratio of the sodium metals to the 1,6-dimethoxy benzene is 0.7-1.2:1; and the reduction temperature is between 15 and 35 DEG C, and the reduction time is between 35 and 48 hours. The technology for preparing the 5-methoxyl-2-tetralone has the advantages of easily obtained reaction raw materials, simple conditions, easy industrialization and high selectivity of the 5-methoxyl-2-tetralone. The 5-methoxyl-2-tetralone is important medical intermediate, and is mainly used for synthesizing medicines for treating Parkinson's disease.
Description
Technical field:
The invention belongs to the preparation method of tetralone compounds.
Background technology:
5-methoxyl group-2-tetralone is very important medicine intermediate, is mainly used in the medicine of synthetic treatment parkinsonism.Market demand is strengthening year by year.The synthetic method of report has:
Method one, by diazo-ketones preparation (Alex A C waits .Journal of Chemistry Society, PerkinTransaction.1,1993, (1): 3-4), having any problem in raw material diazo-ketones source, is catalyzer with rhodium acetate, and price is more expensive.
Method two, by salicylaldhyde preparation (Somnath G waits .Tetrahedron, 1989,45 (5): 1441-1446)
This method total recovery has only 7.5%, and productive rate is too low, and entire synthesis process is used number of chemical reagent, and step is more, and the separation of intermediates is also difficult.Na-Hg agent reduction is polluted big.The annulation of final step carries out at-15 ℃, and industrializing implementation is difficulty.
Method three, by 5-methoxyl group-1-tetralone synthetic (Hoffmann-La Roche Inc.US:4749791,1988-06-07)
Agents useful for same NaBH
4, m-chlorobenzoic acid, MgBr
2All more expensive, and main raw material 5-methoxyl group-1-tetralone is difficult to obtain.
Document (Frank M H waits .Synthesis, and 1980, (8): 621-623) reported the method for synthesizing 5-methoxyl group-2-tetralone by 5-methoxyl group-1-tetralone equally.The step complexity, cost is higher.
Method four, by 1, the 6-dimethoxy-naphthalene is synthetic
This method all is by 1, and the 6-dimethoxy-naphthalene is purified, decomposed and obtain 5-methoxyl group-2-tetralone, concrete technology difference through Birch reduction, hydrolysis, addition.Reaction equation is as follows:
(Jean d ' Angelo waits .Tetrahedron Letters to document, and 1988,29 (35): 4427-4430) report: with metallic lithium reduction 1,6-dimethoxy-naphthalene, cost are too high in liquefied ammonia, trimethyl carbinol medium.
(John W C waits .Journal of Chemistry Society, 1942:689-691 to document; John W.C waits .Journal of Chemistry Society, 1949:1855-1865; Nelson Research ﹠amp; Development.US:4931270 1990-06-05) introduces, with 1, and after 6-dimethoxy-naphthalene, sodium Metal 99.5 mix in dehydrated alcohol, ebuillition of heated, reduction disappears until sodium Metal 99.5.React too violent, 5-methoxyl group-2-tetralone selectivity is low.
(Yoshihiro Hirayama waits .Organic Research ﹠amp to document; Development, 2005,9:30-38) introduce, with 1, after 6-dimethoxy-naphthalene, sodium Metal 99.5 mixed in dehydrated alcohol, 40～85 ℃ of reduction, 5-methoxyl group-2-tetralone selectivity was low.
Take all factors into consideration the method for introducing in the above-mentioned document, comparatively feasible with method four, but high temperature reduction, 5-methoxyl group-2-tetralone selectivity is lower, purification difficult, and yield is lower.
Summary of the invention:
For overcoming 1 in the existing synthetic method, the 6-dimethoxy-naphthalene is through high temperature reduction, methoxyl group-2-tetralone selectivity is lower for preparation 5-, the problem of purification difficult, the present invention proposes a kind of with 1, the 6-dimethoxy-naphthalene 15～35 ℃ of reduction, prepares the preparation technology of 5-methoxyl group-2-tetralone with sodium Metal 99.5 in ethanol, ammonia solution.
Technical scheme:
In reactor, add 1,6-dimethoxy-naphthalene, dehydrated alcohol, liquefied ammonia are stirred to CL.Sodium Metal 99.5 is pressed into silk, adds in the reaction solution in batches and reduce.Control adds sodium speed and heat transfer rate, makes reduction temperature at 15～35 ℃.
Reaction finishes to drip the water dilution in reaction solution, and normal pressure steams the mixture of ethanol, water.Add entry in the still raffinate, agitation and dilution divides oil-yielding stratum.Oil reservoir is mixed with rare concentrated hydrochloric acid, stir, back hydrolysis divides oil-yielding stratum to be 5-methoxyl group-2-tetralone.
In the reduction process,
Dehydrated alcohol and 1, the weight ratio of 6-dimethoxy-naphthalene are 6.0～9.0: 1;
Liquefied ammonia and 1, the weight ratio of 6-dimethoxy-naphthalene are 0.05～0.4: 1;
Sodium Metal 99.5 and 1, the weight ratio of 6-dimethoxy-naphthalene are 0.7～1.2: 1;
Reduction temperature is at 15～35 ℃;
Recovery time was at 35～48 hours;
Embodiment:
Embodiment 1
In the 1000mL four-hole bottle, add 1, the 6-dimethoxy-naphthalene (1,6-OCH
3) 42g, dehydrated alcohol 289g, liquefied ammonia 8.4g is stirred to CL.35g sodium is pressed into filament adds in the reaction solution in batches, add 5g Na at every turn, treat that 5g Na disappears after, continue to add 5g Na again.Control adds Na speed and rate of heating, makes reduction temperature at 25～35 ℃.Begin to finish from adding sodium, need 48 hours approximately to reduction.
In reduced liquid, drip the water dilution, steam the mixture of ethanol, water.Add entry in the still raffinate, agitation and dilution divides oil-yielding stratum.Oil reservoir is mixed with dilute hydrochloric acid, stir, back hydrolysis divides oil-yielding stratum, obtains 5-methoxyl group-2-tetralone, yield 81%.
The gas chromatographic analysis result, 5-methoxyl group-2-tetralone 46.2%; 2-tetralone 7.1%; 1,6-dimethoxy-naphthalene 10.3%; Main by product 21.2%.
Embodiment 2
In the 1000mL four-hole bottle, add 1, the 6-dimethoxy-naphthalene (1,6-OCH
3) 42g, dehydrated alcohol 340g, liquefied ammonia 14.5g is stirred to CL.35g sodium is pressed into filament adds in the reaction solution in batches, add 5g Na at every turn, treat that 5g Na disappears after, continue to add 5g Na again.Control adds Na speed and rate of heating, makes reduction temperature at 15～25 ℃.Begin to finish from adding sodium, need 40 hours approximately to reduction.
In reduced liquid, drip the water dilution, steam the mixture of ethanol, water.Add entry in the still raffinate, agitation and dilution divides oil-yielding stratum.Oil reservoir is mixed with dilute hydrochloric acid, stir, back hydrolysis divides oil-yielding stratum, obtains 5-methoxyl group-2-tetralone, yield 82%.
The gas chromatographic analysis result, 5-methoxyl group-2-tetralone 45.6%; 2-tetralone 6.1%; 1,6-dimethoxy-naphthalene 12.3%; Main by product 20.2%.
Embodiment 3
In the 1000mL four-hole bottle, add 1, the 6-dimethoxy-naphthalene (1,6-OCH
3) 42g, dehydrated alcohol 370g, liquefied ammonia 2.5g is stirred to CL.42g sodium is pressed into filament adds in the reaction solution in batches, add 5g Na at every turn, treat that 5g Na disappears after, continue to add 5g Na again.Control adds Na speed and rate of heating, makes reduction temperature at 25～35 ℃.Begin to finish from adding sodium, need 38 hours approximately to reduction.
In reduced liquid, drip the water dilution, steam the mixture of ethanol, water.Add entry in the still raffinate, agitation and dilution divides oil-yielding stratum.Oil reservoir is mixed with dilute hydrochloric acid, stir, back hydrolysis divides oil-yielding stratum, obtains 5-methoxyl group-2-tetralone, yield 79%.
The gas chromatographic analysis result, 5-methoxyl group-2-tetralone 44.9%; 2-tetralone 7.1%; 1,6-dimethoxy-naphthalene 13.2%; Other by product 22.2%.
Comparative example
In the 1000mL four-hole bottle, add 1, the 6-dimethoxy-naphthalene (1,6-OCH
3) 42g, dehydrated alcohol 289g is stirred to CL, is heated to reflux temperature.35g sodium is pressed into filament adds in the reaction solution in batches, add 5g Na at every turn, treat that 5g Na disappears after, continue to add 5g Na again.Begin to finish from adding sodium, need 2.5 hours approximately to reduction.
In reduced liquid, drip the water dilution, steam the mixture of ethanol, water.Add entry in the still raffinate, agitation and dilution divides oil-yielding stratum.Oil reservoir is mixed with dilute hydrochloric acid, stir, back hydrolysis divides oil-yielding stratum, obtains 5-methoxyl group-2-tetralone, yield 50%.
The gas chromatographic analysis result, 5-methoxyl group-2-tetralone 38.6%; 2-tetralone 26.3%; 1,6-dimethoxy-naphthalene 2.3%; Other by product 27.1%.
The present invention is not limited to the technology described in the embodiment; its description is illustrative; and it is nonrestrictive; authority of the present invention is limited by claim; based on present technique field personnel according to the present invention can change, technology related to the present invention that method such as reorganization obtains, all within protection scope of the present invention.
Claims (2)
1. the preparation technology of 5-methoxyl group-2-tetralone is characterized in that: with 1, the 6-dimethoxy-naphthalene 15～35 ℃ of reduction down, makes 5-methoxyl group-2-tetralone with sodium Metal 99.5 in ethanol, liquefied ammonia medium; Wherein sodium Metal 99.5 is after being pressed into silk, adds in the reaction solution in batches and reduces, and add sodium speed and heat transfer rate by control, makes reduction temperature at 15～35 ℃.
2. the preparation technology of 5-methoxyl group according to claim 1-2-tetralone is characterized in that: dehydrated alcohol and 1 in the reduction process, the weight ratio of 6-dimethoxy-naphthalene are 6.0～9.0: 1; Liquefied ammonia and 1, the weight ratio of 6-dimethoxy-naphthalene are 0.05～0.4: 1; Sodium Metal 99.5 and 1, the weight ratio of 6-dimethoxy-naphthalene are 0.7～1.2: 1; Recovery time in the reduction process is 35～48 hours.
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| CN103880621B (en) * | 2014-04-04 | 2015-08-12 | 南通柏盛化工有限公司 | The method of reducing of preparation 7-methoxy-2-tetralone |
| CN113336633B (en) * | 2021-05-14 | 2022-12-06 | 武汉工程大学 | Synthetic method of 5-hydroxy-2-tetralone |
| CN113233964A (en) * | 2021-05-14 | 2021-08-10 | 武汉工程大学 | Synthesis method of 5-methoxy-2-tetralone |
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| CN1438210A (en) * | 2003-03-13 | 2003-08-27 | 南通莱嘉利化工有限公司 | 7-methoxy-2-telralin-one production method |
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| CN1438210A (en) * | 2003-03-13 | 2003-08-27 | 南通莱嘉利化工有限公司 | 7-methoxy-2-telralin-one production method |
Non-Patent Citations (1)
| Title |
|---|
| Jean d’Angelo et al.."ENANTIOSELECTIVE PREPARATION OF KEY [ABC] INTERMEDIATES FOR STEROID SYNTHESIS THROUGH THE ASYMMETRIC MICHAEL ADDITION PROCESS INVOLVING CHIRAL IMINES.".《Tetrahedron Letters》.1988,第29卷(第35期),4427-4430. |
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